DESCRIPTION: (adapted from the applicants abstract) Mechanoreceptor neurons in soft tissues are activated by tissue stretch, and they signal the tensile stress, as compared to the tensile strain in the stretched tissue. However very little is known about how neurons signal stress. Stress selectivity has been demonstrated only at a gross tissue level, using continuum stress and strain measures. Yet skin is more accurately represented as a composite material with a fiber component that mainly determines its elastic stiffness, and a matrix component that mainly determines its shear modulus and viscoelastic properties. Neuronal responses may be preferentially signaling stress in either component, or may be aggregating stresses occurring in both. Prior observations suggest a hypothesis that 5A2 afferents are coupled to the fiber component, and that RA and C afferents are coupled to the matrix component. This hypothesis will be tested in experiments using mutant mice with abnormal skin mechanical phenotypes. The experimental design will exploit phenotypic differences in both the fiber (i.e., skin elasticity) and matrix (i.e., viscous and shear) components. Alterations in both the fibrous and matrix components of a number of mutant skin phenotypes will be quantified by measuring the material properties in static and dynamic tests. We will determine whether differences in neuron behavior between mutants is paralleled by changes in mechanical variables that reflect the behavior of fiber or matrix components of the skin. In a set of separate, parallel experiments continuing an ongoing project, stretch responses of cutaneous afferents will be studied in isolated skin from primates.